A new study, published in the Journal of Molecular Diagnostics (1), highlights the potential of using long mononucleotide repeat (LMR) markers for characterizing microsatellite instability (MSI) in several tumor types. The paper is a result of a collaborative effort between researchers from Johns Hopkins University and Promega to evaluate the performance of a panel of novel LMR markers for determining MSI status of colorectal, endometrial and prostate tumor samples.
Microsatellite instability (MSI) is the accumulation of insertion or deletion errors at microsatellites, which are short tandem repeats of DNA sequences found throughout the genome. MSI in cancerous cells is the result of a functional deficiency within one or more major DNA mismatch repair proteins (dMMR). PCR-based MSI testing is a commonly used method that can help understand a tumor’s genomic profile as it relates to MMR protein function.
Historically, MSI has been a biomarker associated with Lynch syndrome, the hereditary predisposition to colorectal and certain other cancers. In recent years, research interest in MSI has exploded, driven by the discovery that its presence in tumor tissue can be predictive of a positive response to anti-PD-1 immunotherapies (2,3).
Lynch syndrome is an inherited condition that significantly increases the risk of developing colorectal and other cancers, often at a young age. People with this condition have close to an 80% chance of developing colorectal cancer in their lifetime. It is the most common form of hereditary colon cancer and causes roughly 3% of all colon cancers. The mutations that cause Lynch syndrome are inherited in an autosomal dominant manner— meaning you only need to have one copy of the gene with a Lynch-associated mutation to be at an increased risk.
It is estimated that 1 in every 279 people have inherited a Lynch-associated mutation (1). Yet despite this prevelence, Lynch syndrome is not well known and ~95% of those with the syndrome don’t know they have it (1).
Lynch Syndrome Cause and Detection
Lynch syndrome is caused by mutations that result in the loss of function of one of the four different major mismatch repair proteins. These proteins act as “proof readers” that correct errors in the DNA sequence that can occur during DNA replication. To determine if Lynch syndrome is likely, simple screening tests can be performed on tumor (cancer) tissue to indicate if more specific genetic testing should be considered. One such screening looks for high levels of microsatellite instability (MSI) in the tumor tissue. High microsatellite instability (MSI-H) in tumor tissue is a functional indication that one or more of the major mismatch repair proteins is not functioning properly.
For those who develop colorectal cancer at an early age or have a family history (immediate family member or multiple family members with colorectal cancer or polyps), screening for Lynch syndrome can offer valuable insight for both patients and their family, as well as for their healthcare provider.
New MSI IVD Test for Colorectal Cancer to Help Identify Lynch Syndrome
The newly released Promega OncoMate™ MSI Dx Analysis System is an FDA-cleared IVD Medical Device and can be used to determine the MSI status of colorectal cancer tumors to aid in identifying those who should be further tested for Lynch syndrome. The OncoMate™ MSI Dx Analysis System builds upon the company’s fifteen year history of supporting global cancer researchers with one of the leading standard tests for MSI status detection. The OncoMate™ MSI Dx Analysis System offers an improved formulation while using the same five markers that have become the gold standard for MSI detection in the research community and is referenced in over 140 peer review publications (2,3).
TheOncoMate™ MSI Dx Analysis System is designed to provide physicians with a functional, molecular measurement of the level of DNA mismatch repair deficiency demonstrated within their patient’s colorectal cancer tumor. MSI testing is recommended to identify candidates for further diagnostic testing for Lynch syndrome. (2–4). The System is part of a broader workflow that includes DNA extraction from FFPE tissue samples, quantitation of DNA, amplification of specific microsatellite markers using multiplex PCR, fragment separation by capillary electrophoresis, and data analysis and interpretation software. The OncoMate™ MSI Dx Analysis System is available in certain countries. Visit the OncoMate™ MSI Dx Analysis System webpage to learn more.
Promega previously announced a CE-marked version of the OncoMate™ MSI Dx Analysis System in France, Germany, Austria, Poland, UK, Ireland, Belgium, Netherlands, Luxembourg, Spain, Italy, Switzerland, Denmark, Sweden and Norway.
There are as many different
cancers as there are people with cancer. Unlike infectious diseases, which are
caused by pathogens that are foreign to our bodies (bacteria, viruses, parasites),
cancer cells arise from our body—our own cells gone rogue. Because cancer is a
dysfunction of a person’s normal cells, every cancer reflects the genetic
differences that mark us as individuals. Add to that environmental influences like
diet, tobacco use, the microbiome and even occupation, and the likelihood of
finding a “single” pharmaceutical cure for cancer becomes virtually impossible.
But, while looking for a single cure for all cancers may not be a fruitful activity, defining a best practice for understanding the genetic and protein biomarkers of individual tumors is proving worthwhile.
The 2018 Nobel Prize in Physiology and Medicine was awarded to James P. Allison of the United States and Tasuku Honjo of Japan for their work to identify pathways in the immune system that can be used to attack cancer cells (1). Although immunotherapy for cancer has been a goal for many decades, Dr. Allison and Dr. Honjo succeeded through their manipulation of “checkpoint inhibitor” pathways to target cancer cells.
Immune checkpoint inhibitor drugs have been effective in cancers such as aggressive metastatic melanoma, some lung cancers, kidney, bladder and head and neck cancers. These therapies have succeeded in pushing many aggressive cancers below detectable limits, though these cases are notably not relapse-free or necessarily “cured” (2,3).
One challenge in implementing immunotherapy in a cancer treatment regime is the need to understand the genetic makeup of the tumor. Certain tumors, with specific genetic features, are far more likely to respond to immune checkpoint therapy than others. For this reason, Microsatellite Instability (MSI) analysis has become an increasingly relevant tool in genetic and immuno-oncology research.
By clicking “Accept All”, you consent to the use of ALL the cookies. However you may visit Cookie Settings to provide a controlled consent.
If you are located in the EEA, the United Kingdom, or Switzerland, you can change your settings at any time by clicking Manage Cookie Consent in the footer of our website.
Necessary cookies are absolutely essential for the website to function properly. These cookies ensure basic functionalities and security features of the website, anonymously.
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Analytics".
The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Functional".
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Other.
The cookie is set by GDPR cookie consent to record the user consent for the cookies in the category "Advertisement".
This cookie is set by GDPR Cookie Consent plugin. The cookies is used to store the user consent for the cookies in the category "Necessary".
This cookie is set by GDPR Cookie Consent plugin. The cookie is used to store the user consent for the cookies in the category "Performance".
6 months 2 days
This cookie is set by the provider Media.net. This cookie is used to check the status whether the user has accepted the cookie consent box. It also helps in not showing the cookie consent box upon re-entry to the website.
This cookie is used to store the language preferences of a user to serve up content in that stored language the next time user visit the website.
Analytical cookies are used to understand how visitors interact with the website. These cookies help provide information on metrics the number of visitors, bounce rate, traffic source, etc.
This cookie is associated with Sitecore content and personalization. This cookie is used to identify the repeat visit from a single user. Sitecore will send a persistent session cookie to the web client.
This domain of this cookie is owned by Vimeo. This cookie is used by vimeo to collect tracking information. It sets a unique ID to embed videos to the website.
1 month 18 hours 24 minutes
This cookie is used to calculate unique devices accessing the website.
This cookie is installed by Google Analytics. The cookie is used to calculate visitor, session, campaign data and keep track of site usage for the site's analytics report. The cookies store information anonymously and assign a randomly generated number to identify unique visitors.
This cookie is installed by Google Analytics. The cookie is used to store information of how visitors use a website and helps in creating an analytics report of how the website is doing. The data collected including the number visitors, the source where they have come from, and the pages visted in an anonymous form.
Advertisement cookies are used to provide visitors with relevant ads and marketing campaigns. These cookies track visitors across websites and collect information to provide customized ads.
1 year 24 days
Used by Google DoubleClick and stores information about how the user uses the website and any other advertisement before visiting the website. This is used to present users with ads that are relevant to them according to the user profile.
This cookie is set by doubleclick.net. The purpose of the cookie is to determine if the user's browser supports cookies.
5 months 27 days
This cookie is set by Youtube. Used to track the information of the embedded YouTube videos on a website.
Performance cookies are used to understand and analyze the key performance indexes of the website which helps in delivering a better user experience for the visitors.
This cookies is set by Youtube and is used to track the views of embedded videos.
This is a pattern type cookie set by Google Analytics, where the pattern element on the name contains the unique identity number of the account or website it relates to. It appears to be a variation of the _gat cookie which is used to limit the amount of data recorded by Google on high traffic volume websites.